Urinary incontinence is the involuntary passing of urine. This occurs in an uncontrolled manner if the pressure within the bladder exceeds the pressure required to close the ureter. Causes may include on the one hand an increased internal bladder pressure (e.g. due to detrusor instability) resulting in urgency incontinence, and on the other hand a reduced sphincter pressure (e.g. after childbirth or surgical intervention) resulting in stress incontinence. The detrusor is the collection of coarse bundles forming the multilayered muscular wall of the bladder, whose contraction leads to the discharge of urine, and the sphincter is the constrictor muscle of the urethra. Mixed forms of these types of incontinence as well as so-called overflow incontinence (e.g. in the case of benign prostatic hyperplasia) or reflex incontinence (e.g. following damage to the spinal cord) occur. Further details may be found in Chutka, D. S. and Takahashi P. Y., 1998, Drugs 560: 587-595.
Urinary urgency is the state of increased bladder muscle tension ending in urine discharge (micturition) when the bladder is almost full (or when its capacity is exceeded). This muscle tension acts as a stimulus to urination. Increased urinary urgency is understood in this connection to mean in particular the occurrence of premature or more frequent and sometimes even painful urinary urgency up to so-called dysuria. This consequently leads to a significantly increased frequency of micturition. The causes may include, inter alia, inflammation of the bladder and neurogenic bladder disorders, as well as bladder tuberculosis. However, all causes have not yet been elucidated.
Increased urinary urgency and also urinary incontinence are regarded as extremely unpleasant and there is therefore a clear need to achieve the greatest possible long-term improvement in patients affected by these medical conditions.
Increased urinary urgency and in particular urinary incontinence are normally treated with substances that act on the reflexes of the lower urinary tract (Wein A. J., 1998, Urology 51 (Suppl. 21): 43-47). In general these are medicaments that have an inhibiting effect on the detrusor muscle, which is responsible for the internal bladder pressure. These medicaments include parasympatholytics such as oxybutynin, propiverine or tolterodine, tricyclic antidepressants such as imipramine, or muscle relaxants such as flavoxate. Other medicaments that in particular increase the resistance of the urethra or cervix of the bladder have affinities to α-adrenoreceptors such as ephedrine, to β-adrenoreceptors such as clenbutarol, or are hormones such as estradiol. Also, certain opioids, diarylmethylpiperazines and diarylmethylpiperidines have been described for this medical condition in WO 93/15062.
It should be noted that the treatment of the above generally involves a long-term use of medicaments. In contrast to many other situations in which analgesics are used, patients suffering from urinary incontinence are subjected to very unpleasant but not intolerable discomfort. Accordingly, even more so than with analgesics, care should be taken to avoid side effects if the patient does not wish to exchange one discomfort for another. Furthermore, in the long-term treatment of urinary incontinence analgesic effects are also largely undesirable.